Phase II study of direct intralesional gene transfer of allovectin-7, an HLA-B7/beta 2-microglobulin DNA-liposome complex, in patients with metastatic melanoma

Cutaneous melanoma is one of the most rapidly increasing cancers in the Uni ted States. Because of the lack of effective treatment options and toxiciti es of most chemotherapeutic and radiation regimes, immunotherapies such as vaccination therapy represent an attractive approach for patients with adva nced melanoma. The purpose of this study was to evaluate the response rate, time to progression, and survival of patients with metastatic melanoma tre ated by direct intratumoral injection with Allovectin-7 (a plasmid DNA enco ding the genes HLA-B7 and beta2-microglobulin complexed with a cationic lip id mixture, DMRIE/DOPE. Fifty-two patients with metastatic melanoma were en rolled in this Phase II study. Therapy consisted of six intratumoral inject ions of 10 mug of Allovectin-7 over a 9-week period. Treatment was well tol erated. Treatment-related adverse events were mild to moderate, the most fr equent of which were ecchymosis, pruritus (and/or discomfort at the injecti on site), and pneumothoraces. Regression of the injected lesion was observe d in 18% of patients, including one complete response, three partial respon ses, and five minor responses. An overall response rate of 4% (two partial responses) was documented, and nine patients (18%) maintained stable diseas e for at least 11 weeks. Six patients remained alive 25.1 to 39.4 months fr om their first injection, including two patients with local (injected tumor ) responses and one patient with an overall disease partial response. This study demonstrates that intratumoral administration of Allovectin-7 in meta static melanoma is safe and can produce both responses in injected lesions and in overall disease. Clinical trials optimizing patient selection and co mbining Allovectin-7 with other modalities of therapy are currently ongoing in an effort to improve response rates.